Role of nNOS in regulation of renal function in hypertensive Ren-2 transgenic rats

被引:16
作者
Cervenka, L [1 ]
Kramer, HJ
Maly, J
Vanecková, I
Bäcker, A
Bokemeyer, D
Bader, M
Ganten, D
Mitchell, KD
机构
[1] Inst Clin & Expt Med, Dept Expt Med, Videnska 1958-9, CZ-14000 Prague 4, Czech Republic
[2] Univ Bonn, Dept Med, Med Policlin, Nephrol Sect, D-5300 Bonn, Germany
[3] Max Delbruck Ctr Mol Med, Berlin, Germany
[4] Tulane Univ, Sch Med, Dept Physiol, New Orleans, LA 70112 USA
[5] Ctr Expt Cardiovasc Res, Prague, Czech Republic
关键词
hypertension; transgenic rat; neuronal nitric oxide synthase; renal nerves; renal hemodynamics;
D O I
10.33549/physiolres.930316
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The present study was performed to evaluate the role of neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) during the developmental phase of hypertension in transgenic rats harboring the mouse Ren-2 renin gene (TGR). The first aim of the present study was to examine nNOS mRNA expression in the renal cortex and to assess the renal functional responses to intrarenal nNOS inhibition by S-methyl-L-thiocitrulline (L-SMTC) in heterozygous TGR and in age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). The second aim was to evaluate the role of the renal sympathetic nerves in mediating the renal functional responses to intrarenal nNOS inhibition. Thus, we also evaluated the effects of intrarenal L-SMTC administration in acutely denervated TGR and HanSD. Expression of nNOS mRNA in the renal cortex was significantly increased in TGR compared with HanSD. Intrarenal administration of L-SMTC decreased the glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion and increased renal vascular resistance (RVR) in HanSD. In contrast, intrarenal inhibition of nNOS by L-SMTC did not alter GFR, RPF or RVR and elicited a marked increase in sodium excretion in TGR. This effect of intrarenal L-SMTC was not observed in acutely denervated TGR. These results suggest that during the developmental phase of hypertension TGR exhibit an impaired renal vascular responsiveness to nNOS derived NO or an impaired ability to release NO by nNOS despite enhanced expression of nNOS mRNA in the renal cortex. In addition, the data indicate that nNOS-derived NO increases tubular sodium reabsorption in TGR and that the renal nerves play an important modulatory role in this process.
引用
收藏
页码:571 / 580
页数:10
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